From the state of the art quinoline derivatives are known which are biologically active, for example they exert an antimalarial (J. Med. Chem. 14. 1221, 1971) or antibacterial effect (British patent specification No. 874,980). Among others these earlier references make the development of a broadly applicable method for the preparation of chloromethyl quinoline derivatives justified.
The method used up to now for this purpose (J. Chem. Soc. 123 2882, 1923) is suitable first of all for the preparation of 2-tribromo-methyl-quinoline derivatives (J. Chem. Soc. 1950 628; ibid 1951 1145; ibid 1953 1369) and may be applied for 4-chloro-quinaldine derivatives with a poor yield (J. Med. Chem. 14 1221, 1971).
According to a more advantageous method for the preparation of 2-trichloromethyl-4-chloro-quinoline, 4-quinaldinole was refluxed in the presence of phosphorus pentachloride in phosphoroxy chloride whereupon the product could be isolated from the obtained mixture by the aid of chromatography with a moderate yield (Chem. Ph. Bull 29 1069, 1981). Having condensed ethyl-trichloro-acetyl-acetate with the appropriate aniline, 2-trichloromethyl-4-quinolinole derivatives were obtained with a moderate yield (J. Org. Chem. 31 3369, 1966); there is no known process in the state of the art for the transformation of these compounds to 4-chloro derivatives.
A further disadvantage of the known methods besides the poor to moderate yields is the fact that they may be used only for the preparation of 2-chloromethyl-quinoline derivatives and the selectivity of the reactions is not always sufficient. In certain cases the starting substance (e.g. the trichloro-aceto-acetic ester) is difficult to obtain and is an expensive compound.